English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Tools annual

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Presents the access of premium content as premium feature

Premium Content

Global: Zendy Plus annual

Global: Zendy Free Plan

Background  We evaluated the frequency of naturally occurring resistance associated substitutions (RASs) and their characteristic of polymorphic or non-polymorphic amino acid change to direct acting antivirals (DAAs) in NS5b HCV subtypes 1a and 1b according to different geographic origin of isolates.    Methods  Using a public database we retrieved 738 worldwide NS5b sequences (for which was available the geographic origin) from HCV genotype (G)1 infected patients naive to DAAs. NS5b sequences clustering with G1a were more conserved in regard of RASs than G1b isolates, (14% vs 57% RASs,  P  < 0.0001).    Results  In G1a, RASs were differently distributed between isolates from Europe (24%) and USA, (12%)  P  = 0.0186. In particular, 421 V associated with resistance to non-nucleoside inhibitor beclabuvir was polymorphic in Europe and USA, being detected in 24% and 11% of sequences, respectively,  P  = 0.0140.  In G1b, RASs were found in 45% of sequences from Europe, in 54% of isolates from USA and in 70% of sequences from Asia ( P  = 0.0051).  The 316 N polymorphism was detected in 54% of Asian isolates and at lower frequency, in 28% of isolates from USA and in 20% of European sequences ( P  < 0.0001).    Conclusions  In conclusion, a higher prevalence of RASs in G1b respect to G1a was found and a geographical distribution of RASs and polymorphic aa changes was observed in G1a as well in G1b.  The clinical and therapeutic impact of the geographic distribution of RASs to polymerase inhibitors remains to be established, particularly in patients with virologic failure to DAAs and/or advanced liver disease.

Natural polymorphisms in the resistance associated sites of HCV-G1 NS5B domain and correlation with geographic origin of HCV isolates